The technique of labelling compounds with radionuclides is widely used to monitor the concentration of analytes in biological tissue and fluids. An analyte, e.g., a compound to be analyzed, is synthetically prepared or otherwise labelled with a radionuclide. The labelled analyte is administered to an animal and the level of radioactivity is measured in a body fluid, such as blood, as a function of time. These measurements can provide, for example, estimates of the biological half-life, the absorption rate, the steady state concentration in body fluids and the elimination rate of the analyte and any metabolites resulting therefrom. When these estimates are evaluated in conjunction with other data, such as physiological parameters, they provide insight as to the dosage levels which are efficacious or toxic.
Currently, monitoring the bloodstream concentration of a labelled analyte is a tedious, labor-intensive task with limited time resolution. The labelled analyte is introduced into an experimental animal and blood samples are extracted at various subsequent time intervals. The samples are then analyzed for radioactive content by conventional scintillation counting techniques. This in vitro method is prone to be cumbersome, time-consuming and insensitive. Additionally, if the experimental animal is small, such as a rat or a mouse, the number of samples that can be withdrawn from the animal is limited.
The above mentioned problems and limitations can be substantially alleviated by implanting a "real time" sensor into the bloodstream of the animal. An implantable sensor detects the labelled analyte in vivo, thus eliminating the need to withdraw blood samples. A sensor which is useful for detection of in vivo radiation must be small, compatible with living tissue and of adequate sensitivity to detect low levels of radiation. Biological research utilizing a large experimental animal, such as a dog, will preferably be designed to utilize an analyte which emits low enough levels of radiation to provide a dosage of less than about 2 millicuries (mCu). Research involving a small animal, such as a rat, will preferably be designed to provide a dosage of less than about 1 mCu in order to preserve the viability of the animal.
Miniaturized semiconductor probes for in vivo measurement of beta and gamma radiation are disclosed by Lauber, Nuclear Instruments and Methods 101 (1972) 545-550 Semiconductor sensor devices convert radiation energy directly into electrical current. Low levels of radiation result in low current levels at which semiconductor sensors are susceptible to electrical interference, e.g., noise.
Sensors which use optical methods to detect radiation do not suffer from the same type of signal to noise insufficiencies which effect semiconductor sensors at low radiation levels. Typical optical sensors use a scintillating medium to convert radiation energy into light energy. The light energy is then coupled to an appropriate electro-optical system via an optical waveguide. Swinth, et al., Medical Physics 3 (1976) 109-112 discloses a sensor comprising a thallium-doped sodium iodide crystal surrounded by a diffuse reflector encased in an aluminum shell. Sensors of this design are limited to relatively large diametric proportions in order to assure adequate sensitivity at low radiation levels. Thus implantation into blood vessels is impractical.
It would be highly desirable to provide an in vivo sensor which is sensitive to low levels of radiation, non-toxic and of small enough proportion to be implantable in a blood vessel of any animal, even a small experimental animal such as a rat.